Colombia: Doctoral Excursion, Earth Sciences Department ETH Zurich, August 21 – September 5, 2018

Field guide of Doctoral Excursion to Colombia, co-organized by Luz M. Mejia, R.Ott, L. Echeverria-Pazos, E. Erlanger. Chapter 11: Climate Change Effects on Colombian Biodiversity written by Luz M. Mejia and B. Revels

Candidate gene resequencing in a large bicuspid aortic valve-associated thoracic aortic aneurysm cohort: SMAD6 as an important contributor

Bicuspid aortic valve (BAV) is the most common congenital heart defect. Although many BAV patients remain asymptomatic, at least 20% develop thoracic aortic aneurysm (TAA). Historically, BAV-related TAA was considered as a hemodynamic consequence of the valve defect. Multiple lines of evidence currently suggest that genetic determinants contribute to the pathogenesis of both BAV and TAA in affected individuals. Despite high heritability, only very few genes have been linked to BAV or BAV/TAA, such as NOTCH1, SMAD6, and MAT2A. Moreover, they only explain a minority of patients. Other candidate genes have been suggested based on the presence of BAV in knockout mouse models (e.g., GATA5, NOS3) or in syndromic (e.g., TGFBR1/2, TGFB2/3) or non-syndromic (e.g., ACTA2) TAA forms. We hypothesized that rare genetic variants in these genes may be enriched in patients presenting with both BAV and TAA. We performed targeted resequencing of 22 candidate genes using Haloplex target enrichment in a strictly defined BAV/TAA cohort (n = 441; BAV in addition to an aortic root or ascendens diameter = 4.0 cm in adults, or a Z-score = 3 in children) and in a collection of healthy controls with normal echocardiographic evaluation (n = 183). After additional burden analysis against the Exome Aggregation Consortium database, the strongest candidate susceptibility gene was SMAD6 (p = 0.002), with 2.5% (n = 11) of BAV/TAA patients harboring causal variants, including two nonsense, one in-frame deletion and two frameshift mutations. All six missense mutations were located in the functionally important MH1 and MH2 domains. In conclusion, we report a significant contribution of SMAD6 mutations to the etiology of the BAV/TAA phenotype

Práticas e vivências de Educação Ambiental na Escola de Educação Especial São Francisco de Assis – APAE de Três Passos/RS

O desequilíbrio existente no meio ambiente está comprometendo a qualidade de vida das pessoas. Os educadores são fundamentais no processo de transformação da sociedade e podem contribuir para melhorar a situação. O público alvo da educação especial é o sujeito com deficiência. Como ser um sujeito ecológico é uma opção, a escola e os educadores devem se atentar e criar situações motivacionais que possibilitem o despertar desse sujeito. As escolas, como responsáveis pela formação do cidadão, precisam passar por transformações em suas práticas para enfrentarem os desafios do mundo contemporâneo, especialmente as questões relacionadas ao meio ambiente. Nesse contexto, surge o objetivo deste trabalho, que é proporcionar aos alunos da educação especial práticas e experiências que visem despertar o sujeito ecológico intrínseco em cada um, de maneira a estimular a consciência ambiental e a sustentabilidade. O trabalho foi desenvolvido na Associação de Pais e Amigos dos Excepcionais - APAE de Três Passos-RS, durante os anos de 2018 e 2019. A instituição buscou oferecer práticas que estimulassem o desenvolvimento sociocognitivo de seus educandos, proporcionando dinâmicas de ensino-aprendizagem que os despertassem como sujeitos ecológicos conscientes. A oficina de papel foi uma atividade que possibilitou o desenvolvimento de todas as áreas do conhecimento, além de desenvolver no aluno uma cultura de sustentabilidade socioambiental, motivando-o para a preservação do meio ambiente através da reciclagem do papel e dos elementos que podem ser reaproveitados. Concluiu-se que atividades dinâmicas são excelentes alternativas para envolver, motivar e sensibilizar alunos em relação aos seus direitos e deveres como cidadãos ecológicos

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

A first update on mapping the human genetic architecture of COVID-19

peer reviewe

Das "Emsoz-Projekt": Zur Integration schwieriger Kinder in der Grundschule

Preuss-Lausitz U, Textor A. Das "Emsoz-Projekt": Zur Integration schwieriger Kinder in der Grundschule. In: Platte A, Seitz S, Terfloth K, eds. Inklusive Bildungsprozesse. Bad Heilbrunn: Klinkhardt; 2006: 132-139

Revising the Boundary Element Method for Thermoviscous Acoustics:An Iterative Approach via Schur Complement

The Helmholtz equation is a reliable model for acoustics in inviscid fluids. Real fluids, however, experience viscous and thermal dissipation that impact the sound propagation dynamics. The viscothermal losses primarily arise in the boundary region between the fluid and solid, the acoustic boundary layers. To preserve model accuracy for structures housing acoustic cavities of comparable size to the boundary layer thickness, meticulous consideration of these losses is essential. Recent research efforts aim to integrate viscothermal effects into acoustic boundary element methods (BEM). While the reduced discretization of BEM is advantageous over finite element methods, it results in fully populated system matrices whose conditioning deteriorates when extended with additional degrees of freedom to account for viscothermal dissipation. Solving such a linear system of equations becomes prohibitively expensive for large-scale applications, as only direct solvers can be used. This work proposes a revised formulation for the viscothermal BEM employing the Schur complement and a change of basis for the boundary coupling. We demonstrate that static condensation significantly improves the conditioning of the coupled problem. When paired with an iterative solution scheme, the approach lowers the algorithmic complexity and thus reduces the computational costs in terms of runtime and storage requirements. The results demonstrate the favorable performance of the new method, indicating its usability for applications of practical relevance in thermoviscous acoustics.</p

Identification of immune dominant cytomegalovirus epitopes using quantitative real-time polymerase chain reactions to measure interferon-gamma production by peptide-stimulated peripheral blood mononuclear cells

The identification of HLA restricted immune dominant cytotoxic T cell (CTL) epitopes limits immune therapy. Cytomegalovirus (CMV) disease remains a significant cause of morbidity after allogeneic stem cell transplantation. Adoptive immune therapy using CTLs stimulated with immune dominant CMV pp65 peptides may be effective in preventing CMV disease, but immune dominant CMV peptides have been identified for only a few HLA class I molecules. The purpose of this study was to use a novel molecular system to establish a rapid and precise method to identify new HLA-restricted CMV epitopes. Cytomegalovirus pp65 peptides expected to bind to the HLA-24 molecule were identified with a computer algorithm. Five candidate peptides were screened by direct ex Vivo stimulation of peripheral blood mononuclear cells (PBMCs) from CMV-seropositive HLA-A*2402 individuals, and quantitative real time PCR (qRT-PCR) was used to evaluate CTL responses by measuring interferon-gamma (IFN-gamma) transcripts. One of the five candidate peptides. pp65(341-50) (QYDPVAALFF), induced significant quantities of IFN-gamma mRNA production after 3 hours. PBMCs from CMV-seropositive HLA-A*2402 individuals sensitized in vitro with pp65(341-350) also recognized CMV-infected targets. In conclusion, the measurement of IFN-gamma mRNA by qRT-PCR can be used to detect CTL responses 3 hours after peptide stimulation of a small quantity of PBMCs. This method has an advantage over other methods used to identify immune dominant epitopes in that it does not require in vitro expansion of CTLs with cytokines or virally infected targets. As a result, this method measures naturally induced immune reactions